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Hall, Michael
Publications (10 of 26) Show all publications
Hall, M., Hasegawa, Y., Yoshimura, F. & Persson, K. (2018). Structural and functional characterization of shaft, anchor, and tip proteins of the Mfa1 fimbria from the periodontal pathogen Porphyromonas gingivalis. Scientific Reports, 8, Article ID 1793.
Open this publication in new window or tab >>Structural and functional characterization of shaft, anchor, and tip proteins of the Mfa1 fimbria from the periodontal pathogen Porphyromonas gingivalis
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 1793Article in journal (Refereed) Published
Abstract [en]

Very little is known about how fimbriae of Bacteroidetes bacteria are assembled. To shed more light on this process, we solved the crystal structures of the shaft protein Mfa1, the regulatory protein Mfa2, and the tip protein Mfa3 from the periodontal pathogen Porphyromonas gingivalis. Together these build up part of the Mfa1 fimbria and represent three of the five proteins, Mfa1-5, encoded by the mfa1 gene cluster. Mfa1, Mfa2 and Mfa3 have the same overall fold i.e., two β-sandwich domains. Upon polymerization, the first β-strand of the shaft or tip protein is removed by indigenous proteases. Although the resulting void is expected to be filled by a donor-strand from another fimbrial protein, the mechanism by which it does so is still not established. In contrast, the first β-strand in Mfa2, the anchoring protein, is firmly attached by a disulphide bond and is not cleaved. Based on the structural information, we created multiple mutations in P. gingivalis and analysed their effect on fimbrial polymerization and assembly in vivo. Collectively, these data suggest an important role for the C-terminal tail of Mfa1, but not of Mfa3, affecting both polymerization and maturation of downstream fimbrial proteins.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-144501 (URN)10.1038/s41598-018-20067-z (DOI)000423430400005 ()29379120 (PubMedID)
Available from: 2018-02-05 Created: 2018-02-05 Last updated: 2018-06-09Bibliographically approved
Persson, K., Hall, M., Heidler, T. & Hasegawa, Y. (2018). Structural studies of the five pilin proteins building up the type-V pilus Mfa1 of Porphyromonas gingivalis. Acta Crystallographica - Section A : Foundations and Advances, 74, E425-E425
Open this publication in new window or tab >>Structural studies of the five pilin proteins building up the type-V pilus Mfa1 of Porphyromonas gingivalis
2018 (English)In: Acta Crystallographica - Section A : Foundations and Advances, ISSN 2053-2733, Vol. 74, p. E425-E425Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
International Union of Crystallography, 2018
Keywords
pill, polynraerizaticxaa, bacteria
Identifiers
urn:nbn:se:umu:diva-161753 (URN)10.1107/S2053273318088800 (DOI)000474406600648 ()
Available from: 2019-07-25 Created: 2019-07-25 Last updated: 2019-07-25Bibliographically approved
Kulén, M., Lindgren, M., Hansen, S., Cairns, A. G., Grundström, C., Begum, A., . . . Almqvist, F. (2018). Structure-based design of inhibitors targeting PrfA, the master virulence regulator of Listeria monocytogenes. Journal of Medicinal Chemistry, 61(9), 4165-4175
Open this publication in new window or tab >>Structure-based design of inhibitors targeting PrfA, the master virulence regulator of Listeria monocytogenes
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2018 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 61, no 9, p. 4165-4175Article in journal (Refereed) Published
Abstract [en]

Listeria monocytogenes is a bacterial pathogen that controls much of its virulence through the transcriptional regulator PrfA. In this study, we describe structure guided design and synthesis of a set of PrfA inhibitors based on ring-fused 2-pyridone heterocycles. Our most effective compound decreased virulence factor expression, reduced bacterial uptake into eukaryotic cells, and improved survival of chicken embryos infected with L. monocytogenes compared to previously identified compounds. Crystal structures identified an intraprotein "tunnel" as the main inhibitor binding site (A1), where the compounds participate in an extensive hydrophobic network that restricts the protein's ability to form functional DNA-binding helix−turn−helix (HTH) motifs. Our studies also revealed a hitherto unsuspected structural plasticity of the HTH motif. In conclusion, we have designed 2-pyridone analogues that function as site-A1 selective PrfA inhibitors with potent antivirulence properties.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2018
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:umu:diva-148830 (URN)10.1021/acs.jmedchem.8b00289 (DOI)000432204800027 ()29667825 (PubMedID)2-s2.0-85046422455 (Scopus ID)
Available from: 2018-06-13 Created: 2018-06-13 Last updated: 2018-08-28Bibliographically approved
Mishra, Y., Hall, M., Locmelis, R., Nam, K., Söderberg, C. A. G., Storm, P., . . . Sauer, U. H. (2017). Active-site plasticity revealed in the asymmetric dimer of AnPrx6 the 1-Cys peroxiredoxin and molecular chaperone from Anabaena sp. PCC 7120. Scientific Reports, 7, Article ID 17151.
Open this publication in new window or tab >>Active-site plasticity revealed in the asymmetric dimer of AnPrx6 the 1-Cys peroxiredoxin and molecular chaperone from Anabaena sp. PCC 7120
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 17151Article in journal (Refereed) Published
Abstract [en]

Peroxiredoxins (Prxs) are vital regulators of intracellular reactive oxygen species levels in all living organisms. Their activity depends on one or two catalytically active cysteine residues, the peroxidatic Cys (C-P) and, if present, the resolving Cys (C-R). A detailed catalytic cycle has been derived for typical 2-Cys Prxs, however, little is known about the catalytic cycle of 1-Cys Prxs. We have characterized Prx6 from the cyanobacterium Anabaena sp. strain PCC7120 (AnPrx6) and found that in addition to the expected peroxidase activity, AnPrx6 can act as a molecular chaperone in its dimeric state, contrary to other Prxs. The AnPrx6 crystal structure at 2.3 angstrom resolution reveals different active site conformations in each monomer of the asymmetric obligate homo-dimer. Molecular dynamic simulations support the observed structural plasticity. A FSH motif, conserved in 1-Cys Prxs, precedes the active site PxxxTxxCp signature and might contribute to the 1-Cys Prx reaction cycle.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Structural Biology
Identifiers
urn:nbn:se:umu:diva-143523 (URN)10.1038/s41598-017-17044-3 (DOI)000417354200004 ()29215017 (PubMedID)2-s2.0-85038074530 (Scopus ID)
Note

The original version of this Article contained an error in the title of the paper, where “Anabaena sp. PCC 7120” was incorrectly given as “Anabaena sp. PCC 7210”. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.

Errata: Author Correction: Active-site plasticity revealed in the asymmetric dimer of AnPrx6 the 1-Cys peroxiredoxin and molecular chaperone from Anabaena sp. PCC 7120. Scientifc reports. 2018;8:8658. DOI: 10.1038/s41598-018-26715-8

Available from: 2018-01-04 Created: 2018-01-04 Last updated: 2018-06-15Bibliographically approved
Hall, M., Wagner, R., Tam, L. X., Funk, C. & Persson, K. (2017). The HhoA protease from Synechocystis sp. PCC 6803 – Novel insights into structure and activity regulation. Journal of Structural Biology, 198(3), 147-153
Open this publication in new window or tab >>The HhoA protease from Synechocystis sp. PCC 6803 – Novel insights into structure and activity regulation
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2017 (English)In: Journal of Structural Biology, ISSN 1047-8477, E-ISSN 1095-8657, Vol. 198, no 3, p. 147-153Article in journal (Refereed) Published
Abstract [en]

Abstract Proteases play a vital role in the removal of proteins, which become damaged due to temperature or oxidative stress. Important to this process in the cyanobacterium Synechocystis sp. PCC6803 is the family of Deg/HtrA proteases; HhoA (sll1679), HhoB (sll1427) and HtrA (slr1204). While previous studies have elucidated the structures of Deg/HtrA proteases from Escherichia coli and from the chloroplast of the higher plant Arabidopsis thaliana, no structural data have been available for any Deg/HtrA protease from cyanobacteria, the evolutionary ancestor of the chloroplast. To gain a deeper insight into the molecular mechanisms and regulation of these proteins we have solved the structure of the Synechocystis HhoA protease in complex with a co-purified peptide by X-ray crystallography. HhoA assembles into stable trimers, mediated by its protease domain and further into a cage-like hexamer by a novel interaction between the PDZ domains of opposing trimers. Each PDZ domain contains two loops for PDZ-PDZ formation: interaction clamp one and two (IC1, IC2). IC1 interacts with IC2 on the opposing PDZ domain and vice versa. Our structure shows a peptide bound to a conserved groove on the PDZ domain and the properties of this pocket suggest that it binds substrate proteins as well as the neo C-termini of cleaved substrates. In agreement with previous studies showing the proteolytic activity of HhoA to be activated by Ca2+ or Mg2+, binding of divalent metal ions to the central channel of the trimer by the L1 activation loop was observed.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
sp. PCC 6803, Deg protease, HtrA protease, X-ray structure, Hexamer
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-143748 (URN)10.1016/j.jsb.2016.12.004 (DOI)000403524400001 ()
Funder
Swedish Research Council, 2011-4186Swedish Energy Agency, 2012-005889
Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2018-10-15Bibliographically approved
Hall, M., Wagner, R., Lam, X. T., Funk, C. & Persson, K. (2017). The HhoA protease from Synechocystis sp. PCC 6803: novel insights into structure and activity regulation. Journal of Structural Biology, 198(3), 147-153
Open this publication in new window or tab >>The HhoA protease from Synechocystis sp. PCC 6803: novel insights into structure and activity regulation
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2017 (English)In: Journal of Structural Biology, ISSN 1047-8477, E-ISSN 1095-8657, Vol. 198, no 3, p. 147-153Article in journal (Refereed) Published
Abstract [en]

Proteases play a vital role in the removal of proteins, which become damaged due to temperature or oxidative stress. Important to this process in the cyanobacterium Synechocystis sp. PCC6803 is the family of Deg/HtrA proteases; HhoA (sll1679), HhoB (sll1427) and HtrA (slr1204). While previous studies have elucidated the structures of Deg/HtrA proteases from Escherichia coli and from the chloroplast of the higher plant Arabidopsis thaliana, no structural data have been available for any Deg/HtrA protease from cyanobacteria, the evolutionary ancestor of the chloroplast. To gain a deeper insight into the molecular mechanisms and regulation of these proteins we have solved the structure of the Synechocystis HhoA protease in complex with a co-purified peptide by X-ray crystallography. HhoA assembles into stable trimers, mediated by its protease domain and further into a cage-like hexamer by a novel interaction between the PDZ domains of opposing trimers. Each PDZ domain contains two loops for PDZ-PDZ formation: interaction clamp one and two (IC1, IC2). IC1 interacts with IC2 on the opposing PDZ domain and vice versa. Our structure shows a peptide bound to a conserved groove on the PDZ domain and the properties of this pocket suggest that it binds substrate proteins as well as the neo C-termini of cleaved substrates. In agreement with previous studies showing the proteolytic activity of HhoA to be activated by Ca2+ or Mg2+, binding of divalent metal ions to the central channel of the trimer by the L1 activation loop was observed.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Synechocystis sp. PCC 6803, Deg protease, HtrA protease, X-ray structure, Hexamer
National Category
Biochemistry and Molecular Biology Cell Biology Biophysics
Identifiers
urn:nbn:se:umu:diva-137441 (URN)10.1016/j.jsb.2016.12.004 (DOI)000403524400001 ()27956128 (PubMedID)
Available from: 2017-07-03 Created: 2017-07-03 Last updated: 2018-06-09Bibliographically approved
Zulfugarov, I. S., Tovuu, A., Kim, C.-Y., Vo, K. T., Ko, S. Y., Hall, M., . . . Lee, C.-H. (2016). Enhanced resistance of PsbS-deficient rice (Oryza sativa L.) to fungal and bacterial pathogens. Journal of Plant Biology, 59(6), 616-626
Open this publication in new window or tab >>Enhanced resistance of PsbS-deficient rice (Oryza sativa L.) to fungal and bacterial pathogens
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2016 (English)In: Journal of Plant Biology, ISSN 1226-9239, Vol. 59, no 6, p. 616-626Article in journal (Refereed) Published
Abstract [en]

The 22-kDa PsbS protein of Photosystem II is involved in nonphotochemical quenching (NPQ) of chlorophyll fluorescence. Genome-wide analysis of the expression pattern in PsbS knockout (KO) rice plants showed that a lack of this protein led to changes in the transcript levels of 406 genes, presumably a result of superoxide produced in the chloroplasts. The top Gene Ontology categories, in which expression was the most differential, included 'Immune response', 'Response to jasmonic acid', and 'MAPK cascade'. From those genes, we randomly selected nine that were up-regulated. Our microarray results were confirmed by quantitative RT-PCR analysis. The KO and PsbS RNAi (knockdown) plants were more resistant to pathogens Magnaporthe oryzae PO6-6 and Xanthomonas oryzae pv. oryzae than either the wild-type plants or PsbS-overexpressing transgenic line. These findings suggest that superoxide production might be the reason that these plants have greater pathogen resistance to fungal and bacterial pathogens in the absence of energy-dependent NPQ. For example, a high level of cell wall lignification in the KO mutants was possibly due to enhanced superoxide production. Our data indicate that certain abiotic stress-induced reactive oxygen species can promote specific signaling pathways, which then activate a defense mechanism against biotic stress in PsbS-KO rice plants.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2016
Keywords
Biotic stress tolerance, Microarray, Nonphotochemical quenching, PsbS, Rice, Superoxide
National Category
Botany Genetics
Identifiers
urn:nbn:se:umu:diva-129724 (URN)10.1007/s12374-016-0068-6 (DOI)000389986200006 ()
Available from: 2017-01-10 Created: 2017-01-09 Last updated: 2018-06-09Bibliographically approved
Hall, M., Grundström, C., Begum, A., Lindberg, M. J., Sauer, U. H., Almqvist, F., . . . Sauer-Eriksson, A. E. (2016). Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria. Proceedings of the National Academy of Sciences of the United States of America, 113(51), 14733-14738
Open this publication in new window or tab >>Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria
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2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 51, p. 14733-14738Article in journal (Refereed) Published
Abstract [en]

Infection by the human bacterial pathogen Listeria monocytogenes is mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a cofactor for full activity, and it was recently proposed that glutathione (GSH) could fulfill this function. Here we report the crystal structures of PrfA in complex with GSH and in complex with GSH and its cognate DNA, the hly operator PrfA box motif. These structures reveal the structural basis for a GSH-mediated allosteric mode of activation of PrfA in the cytosol of the host cell. The crystal structure of PrfAWT in complex only with DNA confirms that PrfAWT can adopt a DNA binding-compatible structure without binding the GSH activator molecule. By binding to PrfA in the cytosol of the host cell, GSH induces the correct fold of the HTH motifs, thus priming the PrfA protein for DNA interaction.

Keywords
Listeria, PrfA, activation, glutathione, virulence
National Category
Organic Chemistry Medical Genetics
Identifiers
urn:nbn:se:umu:diva-128915 (URN)10.1073/pnas.1614028114 (DOI)000390044900062 ()
Available from: 2016-12-19 Created: 2016-12-19 Last updated: 2018-06-09Bibliographically approved
Kloppsteck, P., Hall, M., Hasegawa, Y. & Persson, K. (2016). Structure of the fimbrial protein Mfa4 from Porphyromonas gingivalis in its precursor form: implications for a donor-strand complementation mechanism. Scientific Reports, 6, Article ID 22945.
Open this publication in new window or tab >>Structure of the fimbrial protein Mfa4 from Porphyromonas gingivalis in its precursor form: implications for a donor-strand complementation mechanism
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 22945Article in journal (Refereed) Published
Abstract [en]

Gingivitis and periodontitis are chronic inflammatory diseases that can lead to tooth loss. One of the causes of these diseases is the Gram-negative Porphyromonas gingivalis. This periodontal pathogen is dependent on two fimbriae, FimA and Mfa1, for binding to dental biofilm, salivary proteins, and host cells. These fimbriae are composed of five proteins each, but the fimbriae assembly mechanism and ligands are unknown. Here we reveal the crystal structure of the precursor form of Mfa4, one of the accessory proteins of the Mfa1 fimbria. Mfa4 consists of two β-sandwich domains and the first part of the structure forms two well-defined β-strands that run over both domains. This N-terminal region is cleaved by gingipains, a family of proteolytic enzymes that encompass arginine- and lysine-specific proteases. Cleavage of the N-terminal region generates the mature form of the protein. Our structural data allow us to propose that the new N-terminus of the mature protein may function as a donor strand in the polymerization of P. gingivalis fimbriae.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-118663 (URN)10.1038/srep22945 (DOI)000371876900002 ()
Available from: 2016-03-29 Created: 2016-03-29 Last updated: 2018-06-07Bibliographically approved
Uberegui, E., Hall, M., Lorenzo, O., Schröder, W. P. & Balsera, M. (2015). An Arabidopsis soluble chloroplast proteomic analysis reveals the participation of the Executer pathway in response to increased light conditions. Journal of Experimental Botany, 66(7), 2067-2077
Open this publication in new window or tab >>An Arabidopsis soluble chloroplast proteomic analysis reveals the participation of the Executer pathway in response to increased light conditions
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2015 (English)In: Journal of Experimental Botany, ISSN 0022-0957, E-ISSN 1460-2431, Vol. 66, no 7, p. 2067-2077Article in journal (Refereed) Published
Abstract [en]

The Executer1 and Executer2 proteins have a fundamental role in the signalling pathway mediated by singlet oxygen in chloroplast; nonetheless, not much is known yet about their specific activity and features. Herein, we have followed a differential-expression proteomics approach to analyse the impact of Executer on the soluble chloroplast protein abundance in Arabidopsis. Because singlet oxygen plays a significant role in signalling the oxidative response of plants to light, our analysis also included the soluble chloroplast proteome of plants exposed to a moderate light intensity in the time frame of hours. A number of light- and genotype-responsive proteins were detected, and mass-spectrometry identification showed changes in abundance of several photosynthesis-and carbon metabolism-related proteins as well as proteins involved in plastid mRNA processing. Our results support the participation of the Executer proteins in signalling and control of chloroplast metabolism, and in the regulation of plant response to environmental changes.

Keywords
Abiotic stress, acclimation response, chloroplast metabolism, DIGE, light, retrograde signalling, ROS
National Category
Biological Sciences
Identifiers
urn:nbn:se:umu:diva-106375 (URN)10.1093/jxb/erv018 (DOI)000353894100029 ()25740923 (PubMedID)
Available from: 2015-07-15 Created: 2015-07-14 Last updated: 2018-06-07Bibliographically approved
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